The main objectives of this application are to determine: (a) the role of membrane acidic lipids in opiate-receptor interactions and in the pharmacologic actions of opiate; (b) the mechanisms of opiate agonist and antagonist - receptor interactions at the molecular level, using cerebroside sulfate, a membrane acidic lipid, as a model opiate receptor. The rationale of these proposals was derived from the following theoretical and experimental observations: (1) Lipids are predominant and essential molecules of cell membranes and, as such, exert an important structural and functional role within membranes: (2) The recent discovery by several investigators of opiate receptors in nerve membranes; (3) It has been reported that morphine profoundly affects lipid metabolism in the CNS; (4) Molecular models of acidic lipids (e.g., cerebroside sulfate) exhibit structural similarities to the opiate receptor postulated by Beckett and Casey; (5) Preliminary results obtained in our laboratory indicate that the binding of opiates to cerebroside sulfate is saturable, stereospecific, and exhibits high affinity. With over 20 narcotics examined, the binding was closely correlated to their pharmacologic potency; (6) Suggestive evidence has been obtained in vivo that cerebroside sulfates may be involved in the pharmacologic action of opiates. Based on these facts, since the isolation and purification of the endogenous opiate receptor has not been achieved, it is essential to further examine the role of acidic lipids in the pharmacologic action of opiates. Furthermore, preliminary studies with cerebroside sulfate indicate that CS fulfills most of the criteria used to identify opiate receptors in vitro. Therefore, using CS as a model receptor should help to elucidate the mechanism of agonist and antagonist - receptor interaction at the molecular level. Investigations of this nature should also help to clarify which criteria are sufficient as well as necessary for the identification of endogenous opiate receptors.